rs764685377

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6

The ENST00000405460.9(ADGRV1):​c.3943C>A​(p.Gln1315Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

4
14

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.31
Variant links:
Genes affected
ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26693225).
BP6
Variant 5-90653517-C-A is Benign according to our data. Variant chr5-90653517-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 504579.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADGRV1NM_032119.4 linkuse as main transcriptc.3943C>A p.Gln1315Lys missense_variant 20/90 ENST00000405460.9 NP_115495.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADGRV1ENST00000405460.9 linkuse as main transcriptc.3943C>A p.Gln1315Lys missense_variant 20/901 NM_032119.4 ENSP00000384582 P1Q8WXG9-1
ADGRV1ENST00000640403.1 linkuse as main transcriptc.1234C>A p.Gln412Lys missense_variant 10/295 ENSP00000492531
ADGRV1ENST00000504142.2 linkuse as main transcriptn.2709C>A non_coding_transcript_exon_variant 14/145
ADGRV1ENST00000639676.1 linkuse as main transcriptn.1541C>A non_coding_transcript_exon_variant 8/115

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
248980
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135058
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461622
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJan 30, 2018The p.Gln1315Lys variant in ADGRV1 has not been previously reported in individua ls with hearing loss or Usher syndrome, but was identified in 1/15284 African ch romosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitu te.org; dbSNP rs764685377). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Comp utational prediction tools and conservation analyses do not provide strong suppo rt for or against an impact to the protein. In summary, the clinical significanc e of the p.Gln1315Lys variant is uncertain. ACMG/AMP Criteria applied: PM2. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 13, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;T;.
Eigen
Uncertain
0.21
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.69
.;T;T
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.41
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.6
.;N;.
REVEL
Benign
0.16
Sift
Benign
0.081
.;T;.
Sift4G
Benign
0.063
.;T;.
Polyphen
0.94
P;P;.
Vest4
0.64
MutPred
0.45
Gain of methylation at Q1315 (P = 0.0093);Gain of methylation at Q1315 (P = 0.0093);.;
MVP
0.55
MPC
0.057
ClinPred
0.32
T
GERP RS
5.4
Varity_R
0.47
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764685377; hg19: chr5-89949334; API